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. 2020 Jan 14;15(1):e0227676. doi: 10.1371/journal.pone.0227676

Table 2. Summary of clinical and necropsy findings.

Fetal ID ZF1 ZF2 ZF3 ZF4 ZF5 CF3 CF4
Dam ID ZD1 ZD2 ZD3 ZD4 ZD5 CD3 CD4
Inoculum ZIKV ZIKV ZIKV ZIKV ZIKV Saline None
GD of Inoculation 54 55 53 55 53 55 N/A
GD of Delivery 118 126 145 149 148 146 145
GD (PD) of Demise 118 (0) 128 (2) 162 (17) 166 (17) 165 (17) 167 (21) 354 (209)
Pregnancy and Neonatal Outcome Early cervical ripening, pPROM, emergency hysterotomy with fetal euthanasia Early cervical ripening, clinically indicated hysterotomy, neonatal death (septicemia) Elective hysterotomy, live birth, clinically indicated euthanasia Elective hysterotomy, live birth, experimental euthanasia Elective hysterotomy, live birth, experimental euthanasia Elective hyster-otomy, live birth, experimental euthanasia Elective hyster-otomy, live birth, experimental euthanasia
Maternal Utero-placental Pathology Small mono-discoidal placenta; multifocal infarctions, hemorrhage, villous stromal mineralization and perivasculitis Endometritis and myometritis; plasmacytic deciduitis; villous stromal mineralization Multifocal infarctions, acute and chronic hemorrhage, villous fibrin deposition and stromal mineralization Multifocal infarctions, villous fibrin deposition and mineralization, neutrophilic and plasmacytic deciduitis, decidual leukocytoclastic vasculitis Focal infarction, villous fibrin deposition and mineralization, neutrophilic and plasmacytic deciduitis, mild decidual leuko-cytoclastic vasculitis NP Rare stromal mineralization, focal infarction
Neonatal Clinical Presentation N/A Prolonged hypoxemia during resuscitation, hyperglycemia, hypotonia, bradycardia, apnea, cardio-respiratory arrest Seizures, tachypnea, cardiomegaly, axial hypotonia, lower limb weakness, dysphagia, retarded growth Possible mild auditory impairment complicated by presence of earwax NSF NSF NSF
Fetal Gross Pathology NSF Cerebral meningeal and ventricular hemorrhage secondary to sepsis; small cerebellum; chin dermatitis Cardiomegaly with mild dilation of right and left ventricles; reduced brain mass NSF NSF NSF NSF
Fetal CNS Lesions Cerebrum—Multifocal periventricular mineralization; ependymal degeneration; increased apoptosis of neuroprogenitor cell population; increased cells noted in molecular layer of one section, presumed immature neurons (GFAP-/Iba1-/CD45-); increased astrocytes (GFAP+) in molecular layer of cingulate gyrus Cerebellum–Moderate decrease in Purkinje cell population
Spinal cord—Mild to marked rarefaction and edema of white matter, thoracic cord is more affected
Multifocal hemorrhage, edema and necrosis secondary to sepsis. Pathologies atypical to sepsis cannot be conclusively attributed to Zika virus infection:
Cerebrum—Periventricular mineralization, increased apoptosis of neuroprogenitor cells
Cerebellum–Minimal decrease in Purkinje cell population, decreased density of external granular layer
Cerebrum—Ventricular dilation, mild ependymal loss; fewer neuroprogenitor cells
Cerebellum—Attenuation of the external granular cell layer; moderate decrease in Purkinje cell population
Spinal cord—Glial necrosis, white matter, minimal in lumbar cord
Cerebrum—Unilateral periventricular ependymal cell degeneration and loss, focally extensive
Cerebellum—Multifocal, minimal decrease in Purkinje cell population
Cerebellum—Multifocal, moderate decrease in Purkinje cell population and decrease in external granular cell layer
Spinal cord—Swollen myelin sheaths, rare gitter cells and solitary spheroid in cervical cord
Dorsal root ganglion—Scattered, minimal lymphocytic infiltrates
NSF No gross lesions; microscopic lesions not assessed
Fetal Lesions in Other Tissues Urinary bladder—Multifocal, minimal histiocytic infiltrates Skin of chin—Focal, mild, neutrophilic dermatitis
Biceps brachii, left—Hemorrhage and edema secondary to sepsis
Brachioradialis, right—Hemorrhage and edema secondary to sepsis
Heart—Cardiomyopathy, left ventricle, increased cardiomyofiber diameter, cardiomyocyte karyomegaly Heart—Ventricle, cardiomyocyte hypertrophy and karyomegaly, rare Heart—Multifocal, mild to moderate cardiomyocyte vacuolar degeneration and multifocal, mild karyomegaly NSF NSF
Fetal Post-mortem MRI NP T1W and T2W lesions secondary to sepsis Reduced brain volume and surface area NSF NSF NSF NP

NSF = no significant findings, NP = not performed/not assessed, N/A = not applicable.